Genital infection due to Herpes Simplex Virus (HSV2) is one of the most common venereal diseases in the United States today. Genital herpes infections have reached epidemic proportions in the U.S. during the last decade, and other areas of the world, such as Asia, have reported a similar situation. It is estimated that 5 million people suffer from genital herpes infection in the U.S., and that 200,000 to 500,000 uninfected individuals will contract it each year.
The epidemic of genital herpes differs from other common venereal diseases in that the virus currently has no cure. It is a self-limiting disease in itself, but continued recurrences plague the individual throughout his or her lifetime, creating psychological and sexual problems. During the course of primary infection, the virus travels via sensory nerves to the dorsal root ganglia where it can establish a latent state, and from this latent state the virus can reactivate at any time.
Furthermore, a pregnant woman with an active infection at the time of delivery can transmit the virus to her newborn child. About 1,000 children are born each year to herpes infected mothers. Of those delivered vaginally in the presence of viral shedding, 40% become infected. Of those infected, nearly 50% die. The rest will be compromised with infections of the eyes, skin, and viscera, and 25% will be mentally retarded. In addition, there has been a strong association between HSV2 and cervical cancer. Although researchers consider that genital herpes is more responsible for the above conditions, recent reports indicate that oral herpes (HSV1) may affect individuals in a similar manner. See, e.g., Viral Infections of Humans, edited by Alfred S. Evans, Chapter 13 (1984).
Most genital herpes infections are the result of direct contact with infected mucosal or skin lesions. The attack rate from sexual contact is approximately 30 to 50 percent. Clinical manifestations are normally preceded by an incubation period that averages four to seven days. In primary infections, the patients usually experience fever, malaise, and local inguinal adenopathy. Males may experience urethritis while females may suffer vulvitis, vaginitis, and cervicitis. Itching, tension, and pain may precede the development of vesicles that rapidly appear on an erythematous base that contains clear exudate. In most instances, the lesions are localized and consist of groups of three to ten vesicles that crust and heal without scarring after 10 to 14 days. Fifty-three percent of patients with genital herpes experience one or more recurrences per month, 33% have a recurrence every two to four months, and 14% have recurrences less than once every four months. Twenty-four percent of adult patients with oral herpes have a recurrence one or more times per month, 58% once every two to four months, and 18% less than once every four months. (See Medical Clinics of North America, September 1983).
Over the years, various substances have been postulated as medications for the various kinds of herpes. Examples include a mixture of vitamin C and vitamin P for herpes simplex labialis (U.S. Pat. No. 4,049,798), a mixture of kelp and a carrier (U.S. Pat. No. 4,117,120), extract of mountain ash berries (U.S. Pat. No. 4,132,782), a water soluble extract from marine red alga (U.S. Pat. No. 4,162,308), an antiviral lignosulfate (U.S. Pat. No. 4,185,097), 1-amino-2, 4-ethanobicyclo[3, 3, 1]nonane or salts thereof (U.S. Pat. No. 4,230,725), and a suspension of boric acid, tannic acid, and salicylic acid, preferably in an ethanol solvent/carrier (U.S. Pat. No. 4,285,934). As of now, however, there has been no curative drug found to treat genital herpes and there is only one licensed drug usable for its treatment. Acyclovir has been approved in both atopical and oral form by the Food and Drug Administration and is now available with a prescription. When applied topically in initial or primary genital herpes in males and females, the drug has been observed to reduce the duration of viral shedding, hasten the resolution of lesions, and decrease other symptoms. In the form of oral administration, when one Acyclovir capsule (200 mg) was given five times a day for five days, the duration of viral activity, the time of crusting and healing of lesions, and the formation of new lesions were reduced. When taken daily for up to six months (the manufacturer states that it is not advisable to take it for more than six months), it can prevent or reduce recurrences during the period of therapy, but not thereafter. The most common problem in herpes sufferers is still the frequency of recurring genital herpes, which may be disabling to the patients.
In addition, as with any drug, two major factors must be taken into account: (1) emergence of drug-resistant mutant strains of genital herpes; and (2) the cost of the drug. Acyclovir, which is an analog of nucleoside gunosine, is phosphorylated by herpes viruses that induce virus-coded thymidine kinase. It has been shown that thymidine kinase negative mutant strains of herpes viruses exist in nature, and treatment with acyclovir can induce this resistance by selection or mutation. See, e.g., Darby, 50(3) JOURNAL OF VIROLOGY 838 (1984). Thymidine kinase negative mutants of herpes virus strains are shown to be more virulent. A secondary action of acyclovir is inhibition of herpes-induced viral DNA polymerase, but it has been noted tha this mechanism of inhibition by acyclovir is not operative on some strains of herpes viruses.
The cost of the drug is also important. A 15 g tube of acyclovir ointment currently costs $16 to $24. A 200 mg Acyclovir capsule currently costs 70 cents, a five day regimen $17.50, and a six month regimen $630. Recurrent genital herpes infection will require frequent treatments with acyclovir and therefore any relief from symptoms can be quite expensive. In addition, acyclovir is a synthetic analog of nucleoside gunosine. The long-term effects of this synthetic drug are unknown so that in the long run the continued use of the drug may create cost problems as well as reducing its effectiveness.
After extended use, acyclovir is considered toxic so there must remain periods when the drug is not used to avoid a toxicity overload. During these periods, all of the normal problems and symptoms of genital herpes return.
Accordingly, there exists a need for a method of treating genital and oral herpes simplex virus that is natural, non-toxic, reduces the duration of viral shedding, decreases other symptoms, and increases the time between, or eliminates, recurrences.